Stimulation of ⁸⁶Rb⁺ and ³²P_i movements in 3T3 cells by prostaglandins and phorbol esters

Abstract

Abstract The potent tumor promoter tetradecanoyl phorbol acetate (TPA) induces early changes in ion movements analogous to those induced by prostaglandins E 1 and F 2α . Among the earliest changes induced by TPA is a significant increase in 32 P i incorporation within 15 minutes incubation of TPA (10 −8 −10 −6 M) with post‐confluent Swiss 3T3 mouse embryonic fibroblasts. Similarly, the active phorbol ester homolog 4‐;β‐;OH phorbol didecanoate but not the inactive stereoisomeric 4‐β‐OH phorbol didecanoate stimulated 32 P i incorporation. Also, TPA at the above concentrations stimulated 86 Rb + influx shortly after administration. Both fluxes were ouabain‐sensitive in accord with the idea that an early effect of TPA is to alter (Na + + K + )−ATPase activity. Further, prostaglandin E 1 (10 −7 −10 −6 M) and prostaglandin F 2α (3 × 10 −9 −10 −7 M) caused a similar stimulation of 86 Rb + and 32 P i uptake. The finding that water‐soluble prostaglandin F 2α also exhibited stimulatory effects indicated that those hormone‐induced responses are not mediated by solvent interactions. The similar responses of phorbol esters and prostaglandin derivatives suggests that phorbol esters and prostaglandin derivatives may act at common membrane sites The finding that stimulatory effects were observed at discrete times in the logarithmic phase of growth suggests that the activation of membrane receptors may be cell‐cycle dependent.